Grant: Operating Grant

Although cannabis has been used in medicine for centuries, nobody clearly understands how it exerts its effects in humans. Cannabis does much more than increasing appetite: it also decreases pain and inflammation. However, our understanding of how cannabis prevents inflammation is very limited. Over the last decade, two molecules that mimic the effects of cannabis were found in the human body (N-arachidonoyl-ethanolamide (AEA) and 2-arachidonoyl-glycerol(2-AG)). Because of that, they have been termed endocannabinoids. Endocannabinoids contain a lipid named arachidonic acid, which can be transformed into several other lipids that worsen diseases such as arthritis and asthma. Among these lipids are the prostaglandins and the leukotrienes. Endocannabinoids are normally seen as anti-inflammatory while leukotrienes and prostaglandins augment inflammation. Our preliminary data indicate that endocannabinoids can be transformed into leukotrienes. We believe that if we can prevent this transformation, we will decrease inflammation. We will initially characterize how endocannabinoids are transformed into leukotreienes by incubating inflammatory cells with endocannabinoids. We will next evaluate the consequence of such a transformation on the activation state of inflammatory cells by measuring their recruitment, the release of pro-inflammatory molecules, and the ingestion of microbes. Our long term objective is to develop a therapy promoting the anti-inflammatory effects of endocannabinoids. We believe this can be achieved with a compound that would prevent their transformation into arachidonic acid. Such a therapy would increase the quality of life of many Canadians suffering from inflammatory diseases such as asthma and Rheumathoid Arthritis.